Sang Wook Kang

Excellence in robotic thyroid surgery: a comparative study of robot-assisted versus conventional endoscopic thyroidectomy in papillary thyroid microcarcinoma patients.

Objective:To confirm the merits of robotic thyroid surgery by comparing the surgical outcomes of robotic-assisted and conventional endoscopic thyroidectomy in papillary thyroid microcarcinoma (PTMC) patients. Background:Robot-assisted surgical techniques are widely utilized, and substantially, overcome the limitations of conventional endoscopic surgery. Furthermore, recently, robotic procedures were introduced to the thyroidectomy field. Methods:From November 2001 to July 2009, 1150 patients with PTMC underwent endoscopic thyroidectomy using a gasless, trans-axillary approach. Of these patients, 580 underwent a robotic procedure (the robotic group; RG) and 570 a conventional endoscopic procedure (the conventional endoscopic group; EG). These 2 groups were retrospectively compared in terms of their clinicopathologic characteristics, early surgical outcomes, and surgical completeness. Results:Total thyroidectomy was performed more frequently in the RG. Although mean operation times were not statistically different, the mean number of central nodes retrieved was greater in the RG than in the EG. Mean tumor size were not significantly different in the 2 groups, but the RG showed more frequent central node metastasis and capsular invasion. Tumor and nodal statuses in the RG were more advanced than in the EG. Regarding postoperative complications, transient hypocalcemia was more frequent in the RG, but other complication frequencies were not significantly different in the 2 groups. Postoperative serum thyroglobulin levels were similar in 2 groups, and short-term follow-up (1 year) revealed no recurrence by sonography and no abnormal uptake during radioactive iodine therapy in either group. Conclusions:The application of robotic technology to endoscopic thyroidectomy could overcome the limitations of conventional endoscopic surgery during the surgical management of PTMC.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes

BACKGROUND This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER NCT01164176.

Treatment Outcome of Patients with Anaplastic Thyroid Cancer: A Single Center Experience.

Purpose Anaplastic thyroid cancer is known to have a poor prognosis due to its aggressive and rapid metastasis with median survival of less than 6 months. Multimodal treatment involving surgery and chemoradiotherapy has been used to improve the survival of patients. Here, we retrospectively review of treatment outcome of 13 consecutive patients who were treated at a single center. Materials and Methods We retrospectively reviewed medical records of 13 anaplastic thyroid cancer patients who received multidisciplinary treatment between 2006 and 2010. Kaplan-Meier survival curve was used to analyze progression-free survival and overall survival of patients. Results The median patient age at diagnosis was 69 years, and six patients had stage IVc diseases. Eight patients received primary surgery followed by radiotherapy or concurrent chemoradiotherapy (CCRT). Five patients received weekly doxorubicin-based definitive CCRT, but only one patients condition remained stable, while the rest experienced rapid disease progression. The median progression-free survival was 2.8 months (95% CI, 1.2-4.4 months), and the median overall survival was 3.8 months (95% CI, 3.0-4.6 months). Conclusion Patients with anaplastic thyroid cancer showed poor prognosis despite multimodality treatment. Therefore, identification of novel therapeutic targets is warranted to take an effective mode of treatment.

An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer

BACKGROUND This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients. PATIENTS AND METHODS Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety. RESULTS Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events. CONCLUSIONS Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.

Sex Differences in Remifentanil Requirements for Preventing Cough during Anesthetic Emergence

Purpose Target-controlled infusion (TCI) of remifentanil can suppress coughing during emergence from general anesthesia; nevertheless, previous studies under different clinical conditions recommend significantly different effective effect-site concentrations (effective Ce) of remifentanil for 50% of patients (EC50). The differences among these studies include type of surgery and patient sex. In recent years, study of sex differences in regards to anesthetic pharmacology has drawn greater interest. Accordingly, we attempted to determine the effective Ce of remifentanil for preventing cough for each sex under the same clinical conditions. Materials and Methods Twenty female and 25 male ASA physical status I-II grade patients between the ages of 20 and 46 years who were undergoing thyroidectomy were enrolled in this study. The effective Ce of remifentanil for preventing cough was determined for each sex using the isotonic regression method with a bootstrapping approach, following Dixons up-and-down method. Results Isotonic regression with a bootstrapping approach revealed that the estimated EC50 of remifentanil for preventing coughing during emergence was significantly lower in females {1.30 ng/mL [83% confidence interval (CI), 1.20-1.47 ng/mL]} than in males [2.57 ng/mL (83% CI, 2.45-2.70 ng/mL)]. Mean EC50 in females was also significantly lower than in males (1.23±0.21 ng/mL vs. 2.43±0.21 ng/mL, p<0.001). Mean arterial pressure, heart rate, and respiratory rate over time were not significantly different between the sexes. Conclusion When using remifentanil TCI for cough prevention during anesthetic emergence, patient sex should be a considered for appropriate dosing.

Study of peripheral BRAFV600E mutation as a possible novel marker for papillary thyroid carcinomas

The BRAFV600E mutation can be detected peripherally in the serum of patients with thyroid cancer. The purpose of this study was to establish the value of detecting the peripheral BRAFV600E mutation as a serum tumor marker in this population.

Gasless transaxillary endoscopic thyroidectomy: a decade on.

Purpose: In 2001, the authors developed a novel method of gasless transaxillary endoscopic thyroidectomy (ET) and have now performed >1000 operations. This review was performed to document surgical outcomes after 10 years of experience with this technique and to determine what the role of ET has in the current era. Patients and Methods: All patients who underwent elective ET using the gasless transaxillary approach from November 2001 to December 2010 were evaluated. Patient demographics, surgical data, histologic analysis results, and complications were recorded and analyzed. Results: A total of 1085 patients underwent ET during the study period. Mean patient age was 36.9±9.7 years; the gender ratio was 1:49 (male:female). There were 228 benign thyroid tumor cases and 857 thyroid malignancies. Trend analysis showed a progressive increase in case numbers per month until the end of 2007, followed by a steady decline. There were 175 total thyroidectomy cases and 910 cases of less-than-total thyroidectomy. Mean overall operating time was 132.92±48.6 minutes, and the overall complication rate was 13.5%. The most common complications were: transient hypocalcemia (6.3%), transient hoarseness (3.9%), hematoma (0.4%), permanent hypocalcemia (0.1%), and permanent recurrent laryngeal nerve injury (0.2%). Conclusions: Gasless ET is comparable to open thyroidectomy in terms of early surgical outcomes and complications, and it bridges the gap between conventional open surgery and robotic transaxillary thyroidectomy.

Is focused parathyroidectomy appropriate for patients with primary hyperparathyroidism

Purpose The aim of this study was to determine whether focused or complete parathyroidectomy was more appropriate and to compare follow-up data in primary hyperparathyroidism (PHPT). Methods We retrospectively analyzed 225 operations for PHPT at Yonsei University Health System between 2000 and 2012. After excluding 93 patients, the remaining 132 were divided into 2 groups: those who underwent focused parathyroidectomy (FP) and those who underwent conventional parathyroidectomy (CP). We compared clinicopathological features; preoperative calcium, parathyroid hormone (PTH), phosphorus, vitamin D, 24-hour urine calcium, and alkaline phosphatase levels; postoperative calcium and PTH levels; pathologic diagnosis; multiplicity; and results of a localization study between the 2 groups. Results There was no significant difference in the rates of development of postoperative persistent hyperparathyroidism (1/122 FP patients and 1/10 CP patients) between the 2 groups due to a technical reason (FP 0.8% vs. CP 10.0%, P = 0.146). Multiglandular disease (MGD) was uncommon in all cases (6 of 132, 4.5%). All MGD cases were diagnosed using a preoperative localization study. Sestamibi scan and ultrasonography sensitivity were 94.2% and 90.2%, respectively. Conclusion We suggest that FP is appropriate in PHPT, except in cases of MGD if detected before the operation using preoperative imaging. Knowledge of hereditary PHPT and improved preoperative localization studies, such as high-resolution ultrasonography, contributed to the decision to perform FP rather than CP in all cases of unilateral results of the localizing study.

Preventive Effect of Human Acellular Dermal Matrix on Post-thyroidectomy Scars and Adhesions: A Randomized, Double-Blinded, Controlled Trial

BACKGROUND Acellular dermal matrix (ADM) has been used for antiadhesion formation along with wound healing in various surgical fields. OBJECTIVE The aim is to assess the efficacy of ADM implantation in the prevention of postoperative scars and adhesions after conventional, open, total thyroidectomy. MATERIALS AND METHODS Forty-four patients with papillary thyroid carcinoma undergoing thyroidectomy were randomly assigned to the study (ADM implantation) or control group (without ADM). Global photographic assessment, Vancouver scar scale (VSS), objective scar assessment, and swallowing impairment index were assessed at baseline, immediately after surgery, and at 1 and 2 months after surgery. RESULTS Nineteen control and 20 study group participants completed the study. The mean VSS score of the study group was significantly lower than the controls at both 1 month (3.06 ± 1.25 vs 4.41 ± 1.54, respectively) and 2 months (2.76 ± 1.56 vs 4.35 ± 1.58, respectively) after surgery. Scar quality measures (mean melanin and erythema indexes) were significantly lower in the study group compared with controls. Study group participants had significantly lower swallowing impairment scores than controls. The mean postoperative hospitalization of both groups was not significantly different. CONCLUSION Acellular dermal matrix–assisted implants appear to improve post-thyroidectomy scar and swallowing impairments without delays in operation time.

KSR1 is coordinately regulated with Notch signaling and oxidative phosphorylation in thyroid cancer.

Kinase suppressor of RAS1 (KSR1) is a scaffold protein implicated in RAS-mediated RAF activation. However, the molecular function of KSR in papillary thyroid cancer (PTC) is unknown. Thus, this study aimed to characterize the role of KSR1 in patients with PTC. qRT-PCR and immunohistochemistry (IHC) revealed inter-tumor heterogeneities in the expression of KSR1 in PTC tissues. Interestingly, BRAFV600E-positive PTC showed higher KSR1 mRNA expression than BRAFV600E-negative PTC (P<0.001). Gene Set Enrichment Analysis (GSEA) using public repositories showed that high KSR1 expression coordinately upregulated Notch signaling (nominal P=0.019, false discovery rate (FDR) q-value=0.165); this finding was supported by GeneNetwork analysis, indicating that KSR1 expression is positively correlated with NOTCH1 expression (ρ=0.677, P=6.15×10(-9)). siRNA against KSR1 (siKSR1) significantly decreased ERK phosphorylation induced by BRAFV600E, resulting in reduced expression of NOTCH1 and HES1, targets of Notch signaling. GSEA revealed that high KSR1 expression was also associated with downregulation of genes related to oxidative phosphorylation (OxPhos). Consistent with this, electron microscopy showed that PTCs with high KSR1 expression exhibited structural defects of the mitochondrial cristae. Furthermore, siKSR1-transfected BCPAP and 8505C cells generated fewer colonies in colony-forming assays. In addition, GSEA showed that high expression of KSR2 and connector enhancer of KSR1 (CNKSR1) also coordinately upregulated Notch signaling (KSR2: nominal P=0.0097, FDR q-value=0.154 and CNKSR1: nominal P<0.0001, FDR q-value=0.00554), and high CNKSR2 was associated with downregulation of the OxPhos gene set (nominal P<0.0001, FDR q-value <0.0001). In conclusion, KSR1 is coordinately regulated with Notch signaling and OxPhos in PTC, because its scaffold function might be required to sustain the proliferative signaling and metabolic remodeling associated with this type of cancer.